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Following peripheral nerve injury (PNI), Wallerian degeneration (WD) in the distal stump can generate a microenvironment favorable for nerve regeneration. Brief low-frequency electrical stimulation (ES) is an effective treatment for PNI, but the mechanism underlying its effect on WD remains unclear. Therefore, we hypothesized that ES could enhance nerve regeneration by accelerating WD. To verify this hypothesis, we used a rat model of sciatic nerve transection and provided ES at the distal stump of the injured nerve. The injured nerve was then evaluated after 1, 4, 7, 14 and 21 days post injury (dpi). The results showed that ES significantly promoted the degeneration and clearance of axons and myelin, and the dedifferentiation of Schwann cells. It upregulated the expression of BDNF and NGF and increased the number of monocytes and macrophages. Through transcriptome sequencing, we systematically investigated the effect of ES on the molecular processes involved in WD at 4 dpi. Evaluation of nerves bridged using silicone tubing after transection showed that ES accelerated early axonal and vascular regeneration while delaying gastrocnemius atrophy. These results demonstrate that ES promotes nerve regeneration by accelerating WD and upregulating the expression of neurotrophic factors., (© 2022 Wiley Periodicals LLC.)

Functional impairment after spinal cord injury (SCI) is attributed to neuronal cell necrosis death and axonotmesis, with further worsening caused by the accompanying apoptosis of myelin-forming oligodendrocytes (OLGs). However, it is unclear as to how much OLG apoptosis contributes to functional impairment. To address this issue, we used transgenic mice characterized by the targeted expression of p35, a broad-spectrum caspase inhibitor, in OLGs using the cre/loxP system (referred to as cre/p35 transgenic mice). In this study, we examined the motor function and histopathologic changes after a contusive thoracic spinal cord injury in the cre/p35 transgenic mice. A larger number of OLGs and a lesser extent of demyelination were observed after SCI in the cre/p35 transgenic mice than in the control cre mice, which did not carry the p35 transgene. Furthermore, the motor function of the hindlimbs recovered to a significantly better degree in the cre/p35 transgenic mice than in the control cre mice. Thus, the inhibition of OLG apoptosis decreased the extent of functional impairment after SCI. These findings suggest that the inhibition of OLG apoptosis may be a potential treatment for SCI., ((c) 2005 Wiley-Liss, Inc.)

If Schwann cell transplantation is to be used as a therapy for demyelinating disease, it is important to know if the number of transplanted cells and their transplantation site affects the extent of remyelination. Primary Schwann cell cultures were obtained from neonatal rat sciatic nerve, purified, and expanded using bovine pituitary extract and forskolin. Areas of persistent demyelination were created in the dorsal funiculus of the thoracolumbar spinal cord of rats by injecting ethidium bromide into white matter exposed to 40 Gy of X-irradiation, and a high and low number of Schwann cells were transplanted, into either the area of demyelination or the dorsal funiculus cranial to the area of demyelination. Animals were perfused 4 weeks after transplantation. After injection of 4 x 10(4) cells into the area of demyelination, the area of Schwann cell remyelination was 0.88 +/- 0.16 mm(2), while following the injection of 3 x 10(3) cells it was significantly smaller, 0.29 +/- 0.09 mm(2). After implantation of Schwann cells 1-3 mm (mean 2.5 mm) cranial to the area of demyelination, only one of the eight animals (a high-dose animal) showed extensive Schwann cell remyelination. In this animal, the cells were transplanted within 1 mm of the area of demyelination, well within the length of tissue over which cells are passively spread by the injection procedure (1-3 mm). Our results show that significant numbers of transplanted Schwann cells are not attracted through normal tissue to areas of demyelination and when transplanted into areas of demyelination the extent of myelination is related to the number of Schwann cells transplanted., (Copyright 2000 Wiley-Liss, Inc.)